Managing antihistamine impairment in patients with allergic rhinitis

SELECTED ARTICLES FROM THE RECENT LITERATURE 2003

8/14/03

Managing antihistamine impairment in patients with allergic rhinitis

Summary
Antihistamines (AH) are among the medications most frequently obtained by prescription or over the counter (OTC) in the USA, particularly in the treatment of allergic rhinitis (AR), a very common disorder. However, there is a significant incidence of adverse effects of AH with a number of misconceptions about AH seen in many patients and some physicians. The adverse effects of AH were recently reviewed in a round table discussion by experts in the pharmacology and clinical studies of AH effects.

AH act as inverse agonists, stabilizing an inactive form of the histamine (H1) receptor and some other receptors such as the muscarinic receptors. The action on non-histamine receptors may lead to adverse. The ratio of the AH dose that induces toxicity divided by the dose that produces the desired beneficial effects (called the therapeutic index) varies with different AH agents.

First generation AH (FGA) such as diphenhydramine (Benadryl and generic versions) and chlorpheniramine are the 6th and 12th most commonly used medication, respectively, in the USA. Because such FGA are lipophilic, they penetrate fairly readily into the CNS and interfere with histamine effects there resulting in sedation and impairment of cognitive functions.

Second generation AG (SGA) are relatively lipophobic with decreased penetration into the CNS than FGA. Therefore, there is less sedative effects of usual therapeutic doses. However, cetirizine (Cet, Zyrtec) penetrates more into the CNS with greater potential for sedation than does loratadine (Lor, Claritin) and fexofenadine (Fex. Allegra) in usual doses. If one compares the sedative properties of SGA with Lor effects arbitranly set at 1.0, the sedation odds ratio for Fex is 0.63, for acrivastine is 2.79 and for Cet is 3.53. SGA are more specific for the histamine receptor than are the FGA, with less potential for adverse side-effects due to binding to muscarine and other receptors. However, there are differences among the SGA in their therapeutic index (defined above), of importance when greater than usual recommended doses are taken (a common problem with some patients). Thus, there is increased sedation following consumption of 20 mg of Lor or Cet (twice the usual adult dose) but no increased sedation following consumption of 320 mg of Fex (also twice the usual therapeutic dose).

Impairment of cognitive function may occur with or without sedation. In the latter case, the patient may not realize that he/she is impaired when driving, etc. Such impairment is very common with FGA and to some degree with .Cet but not with Fex or with lower doses of Lor. Lor also has a slower onset of AH action (1-3 hours), as compared to Fex and Cet, an important consideration when taken after the onset of symptoms of AR. Fex and Cet appear to be equally effective in the treatment of AR.

Reference
Allergy Clin Immunol 2003;111:S835-42

Editor’s Comments
This is a highly informative, well balanced discussion by some of the leading experts in AH effects. This information dispels some common misconceptions (e.g., that individuals commonly lose the sedative effects of FGA with continued use). Well worth reading.